Vaccinal Effect of HBsAg Monoclonal Ab VIR-3434 in Chronic Hepatitis B Infection [VISION]

Hepatitis B, Chronic Clinical Trial

Official title:

Phase II Investigator-Initiated Study to Understand the Vaccinal Effect of HBsAg Monoclonal Ab VIR-3434 in Chronic Hepatitis B Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06216470
• Other study ID #: 23-5492
• Status: Recruiting
• Phase: Phase 2
• Start date: March 13, 2024
• Est. completion date: December 2029

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: Jordan Feld, MD
• Phone: 416-340-4584
• Email: jordan.feld[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II Investigator-Initiated Study to understand the vaccinal effect of HBsAg monoclonal Ab VIR-3434 in chronic hepatitis B infection. The purpose of this study is to test VIR-3434, an experimental drug that specifically targets the HBsAg of hepatitis B virus, to clear it from the body. This is an open label study and there is no placebo used in this study. All participants will receive the VIR-3434 for 48 weeks and then follow up in the study for 48 weeks. A total duration of approximately 104 weeks including screening period for the entire study.

Description:

The objective of this study is to evaluate the vaccinal effect of VIR-3434 in chronic HBeAg-negative hepatitis B (CHB) patients suppressed on nucleos(t)ide analogue therapy. Total 15 patients will be enrolled at single site. The participants will receive VIR-3434 300 mg subcutaneous injection every 4 weeks x 48 weeks and then follow up for 48 weeks. Total three Fine-needle aspiration (FNA) procedure will be performed during the study: before treatment, 3 days after the first injection and 3 days after the week24 injection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2029
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Age = 18 to =60 years

2. Chronic HBV infection with evidence of HBsAg-positivity x > 6 months

3. Quantitative HBsAg 500 - 10,000 IU/mL

4. HBeAg-negative

5. On stable nucleos(t)ide therapy >1 year

6. HBV DNA < 60 IU/mL on 2 occasions at least 12 weeks apart

7. ALT = 45 U/L on 2 occasions at least 12 weeks apart

8. Female subjects must have a negative pregnancy test or confirmation of postmenopausal status. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and on Day 1, cannot be breast feeding, and must be willing to use highly effective methods of contraception 14 days before study drug administration through the study participation. Female subjects must also agree to refrain from egg donation and in vitro fertilization from the time of study drug administration through the study participation.

9. Male subjects with female partners of child-bearing potential must agree to meet 1 of the following contraception requirements from the time of study drug administration through the study participation: documentation of vasectomy or azoospermia, or male condom use plus partner use of 1 of the contraceptive options listed for contraception for WOCBP. Male subjects must also agree to not donate sperm from the time of study drug administration through the study participation.

10. Able and willing to sign informed consent

Exclusion Criteria:

1. History of cirrhosis as evidenced by prior Liver Elastography (Fibroscan) > 12 kilopascals (kPa), liver biopsy (F4 by METAVIR) or clinical evidence of decompensation (ascites, hepatic encephalopathy)

2. History of or current hepatocellular carcinoma

3. Hepatitis C Virus (HCV) RNA or anti-Hepatitis D Virus (HDV) positive

4. HIV co-infection

5. Pregnancy or lactation

6. Alanine Aminotransferase (ALT) > 45 U/L

7. History of chronic liver disease other than HBV aside from fatty liver documented only on US

8. Use of peginterferon therapy for HBV infection within past 12 months

9. Use of chronic immunosuppressive medications at a dose equivalent to 10 mg daily of prednisone or greater within past 6 months

10. Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in previous 6 months, malignancy other than non-melanoma skin cancer in previous 5 years, immunodeficiency syndrome

11. Subject has received any investigational drug (including any investigational vaccines) within 90 days or 5 half-lives (whatever is longer) before screening for this study or is currently enrolled in an investigational study

12. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments, such as liver FNAs

13. Platelet count < 120,000,000,000/L

14. The International Normalised Ratio (INR) > 1.3

15. Bilirubin > 40 µmol/L

16. Hemoglobin < 110 g/dL for women or 120 g/dL for men

17. estimated Glomerular Filtration Rate (eGFR) < 45 cc/min

18. Alpha Fetoprotein (AFP) > 50 ng/mL

19. Prior liver or other solid organ transplantation

20. Patients on anticoagulation therapy or with any bleeding diathesis

21. Patients with hemoglobinopathy (thalassemia, sickle cell disease etc)

22. Other significant liver disease: alcoholic liver disease, autoimmune hepatitis, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson Disease or alpha-1 antitrypsin deficiency - as documented in clinical history

23. Unable to provide informed consent

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• VIR-3434
VIR-3434 is a human monoclonal antibody that binds the antigenic loop present in all forms of the surface envelope protein (small, middle, and large HBsAg).

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in log Quantitative HBsAg		from baseline through study completion, an average of 2 year
Secondary	Absolute and change of Hepatitis B Virus (HBV) RNA		from baseline through study completion, an average of 2 year
Secondary	Absolute and change of HBV core-related Ag		from baseline through study completion, an average of 2 year
Secondary	Proportion of subjects with HBsAg loss		from baseline through study completion, an average of 2 year
Secondary	Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) with study treatment	Frequency of AEs and SAEs with VIR-3434 administration in combination with NA therapy for CHB	from baseline through study completion, an average of 2 year
Secondary	Frequency of AEs and SAEs due to hepatic FNA		from baseline through study completion, an average of 2 year